Trial Outcomes & Findings for A Clinical Study to Evaluate Z7200 (Budesonide/Formoterol) Pharmacokinetics Profile in Healthy Volunteers (NCT NCT02237508)

NCT ID: NCT02237508

Last Updated: 2022-02-23

Results Overview

Area under the plasma concentration-time curve from time zero to the last detectable level calculations were performed using the linear trapezoidal rule. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 90 participants
• Primary outcome timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)
• Results posted on: 2022-02-23

Participant Flow

Subjects were screened for eligibility -28 to -2 days prior to the first treatment period. On Day -1 of the first treatment period, i.d. before randomization, subjects were trained on both the RS01 and Symbicort Turbohaler devices.

Subjects had to have an adequate inspiratory flow rate and be able to use both inhalers. Subjects who continued to meet all entry criteria on Day -1 of treatment Period 1 and with an inspiratory flow rate of ≥60 L/min and proper device use entered the treatment phase.

Participant milestones

Measure	A-B1-B2-C-D Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	B1-C-A-D-B2 Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	C-D-B1-B2-A Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	D-B2-C-A-B1 Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	B2-A-D-B1-C Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	D-C-B2-B1-A Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	B2-D-A-C-B1 Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	A-B2-B1-D-C Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	B1-A-C-B2-D Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	C-B1-D-A-B2 Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).
Overall Study STARTED	9	9	9	9	9	9	9	9	9	9
Overall Study A	9	6	8	8	9	8	8	9	9	9
Overall Study B1	9	9	9	8	9	9	9	9	9	9
Overall Study B2	9	6	9	9	9	9	9	9	8	9
Overall Study C	9	8	9	8	9	9	9	9	9	9
Overall Study D	9	6	9	9	9	9	9	9	8	9
Overall Study COMPLETED	9	6	8	8	9	8	8	9	8	9
Overall Study NOT COMPLETED	0	3	1	1	0	1	1	0	1	0

Reasons for withdrawal

Measure	A-B1-B2-C-D Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	B1-C-A-D-B2 Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	C-D-B1-B2-A Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	D-B2-C-A-B1 Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	B2-A-D-B1-C Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	D-C-B2-B1-A Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	B2-D-A-C-B1 Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	A-B2-B1-D-C Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	B1-A-C-B2-D Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	C-B1-D-A-B2 Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).
Overall Study Withdrawal by Subject	0	2	0	1	0	1	1	0	1	0
Overall Study Physician Decision	0	1	0	0	0	0	0	0	0	0
Overall Study Protocol Violation	0	0	1	0	0	0	0	0	0	0

Baseline Characteristics

A Clinical Study to Evaluate Z7200 (Budesonide/Formoterol) Pharmacokinetics Profile in Healthy Volunteers

Baseline characteristics by cohort

Measure	A-B1-B2-C-D n=9 Participants Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	B1-C-A-D-B2 n=9 Participants Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	C-D-B1-B2-A n=9 Participants Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	D-B2-C-A-B1 n=9 Participants Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	B2-A-D-B1-C n=9 Participants Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	D-C-B2-B1-A n=9 Participants Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	B2-D-A-C-B1 n=9 Participants Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	A-B2-B1-D-C n=9 Participants Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	B1-A-C-B2-D n=9 Participants Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	C-B1-D-A-B2 n=9 Participants Subjects were dosed on Day 1 of each treatment period with one of the following 5 treatments according to the randomization schedule using a Williams Latin Square design: 1. Treatment A: Z7200 without oral activated charcoal 2. Treatment B1: Symbicort 1 without oral activated charcoal 3. Treatment B1: Symbicort 2 without oral activated charcoal 4. Treatment C: Z7200 with oral activated charcoal 5. Treatment D: Symbicort with oral activated charcoal A washout period ≥5 days followed treatment periods 1 to 4. Z7200 without activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A). Symbicort Turbohaler without activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2). Z7200 with activated charcoal: 160 ug budesonide and 4.5 ug formoterol, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C). Symbicort Turbohaler with activated charcoal: 320 ug budesonide and 9 ug formoterol, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation, with charcoal blockade (Treatment D).	Total n=90 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=5 Participants	9 Participants n=7 Participants	9 Participants n=5 Participants	9 Participants n=4 Participants	9 Participants n=21 Participants	9 Participants n=8 Participants	9 Participants n=8 Participants	9 Participants n=24 Participants	9 Participants n=42 Participants	9 Participants n=42 Participants	90 Participants n=42 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Age, Continuous	29.0 years STANDARD_DEVIATION 7.9 • n=5 Participants	24.7 years STANDARD_DEVIATION 6.5 • n=7 Participants	27.2 years STANDARD_DEVIATION 6.0 • n=5 Participants	28.1 years STANDARD_DEVIATION 7.4 • n=4 Participants	26.3 years STANDARD_DEVIATION 7.6 • n=21 Participants	29.8 years STANDARD_DEVIATION 8.5 • n=8 Participants	28.0 years STANDARD_DEVIATION 7.6 • n=8 Participants	28.3 years STANDARD_DEVIATION 5.9 • n=24 Participants	27.8 years STANDARD_DEVIATION 8.9 • n=42 Participants	36.2 years STANDARD_DEVIATION 5.0 • n=42 Participants	28.5 years STANDARD_DEVIATION 7.4 • n=42 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants	5 Participants n=8 Participants	5 Participants n=8 Participants	3 Participants n=24 Participants	5 Participants n=42 Participants	4 Participants n=42 Participants	37 Participants n=42 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	8 Participants n=4 Participants	7 Participants n=21 Participants	4 Participants n=8 Participants	4 Participants n=8 Participants	6 Participants n=24 Participants	4 Participants n=42 Participants	5 Participants n=42 Participants	53 Participants n=42 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=8 Participants	1 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	3 Participants n=42 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	1 Participants n=8 Participants	0 Participants n=24 Participants	1 Participants n=42 Participants	3 Participants n=42 Participants	5 Participants n=42 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	9 Participants n=7 Participants	9 Participants n=5 Participants	9 Participants n=4 Participants	8 Participants n=21 Participants	8 Participants n=8 Participants	7 Participants n=8 Participants	9 Participants n=24 Participants	8 Participants n=42 Participants	6 Participants n=42 Participants	80 Participants n=42 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants	2 Participants n=42 Participants
Region of Enrollment United Kingdom	9 participants n=5 Participants	9 participants n=7 Participants	9 participants n=5 Participants	9 participants n=4 Participants	9 participants n=21 Participants	9 participants n=8 Participants	9 participants n=8 Participants	9 participants n=24 Participants	9 participants n=42 Participants	9 participants n=42 Participants	90 participants n=42 Participants

PRIMARY outcome

Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)

Population: PK population included subjects who had received both test and reference for at least one dose of each treatment without or with oral charcoal.

Area under the plasma concentration-time curve from time zero to the last detectable level calculations were performed using the linear trapezoidal rule.

Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

Outcome measures

Measure	Treatment A n=83 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=164 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=84 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=84 Participants Symbicort with charcoal (320 ug budesonide)
AUC0-t of Budesonide With and Without Charcoal Blockade	1870 pg*h/mL Geometric Coefficient of Variation 20.2	1360 pg*h/mL Geometric Coefficient of Variation 49.4	1810 pg*h/mL Geometric Coefficient of Variation 22.3	1330 pg*h/mL Geometric Coefficient of Variation 52.3

PRIMARY outcome

Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)

Population: PK population included subjects who had received both test and reference for at least one dose of each treatment without or with oral charcoal.

Area under the plasma concentration-time curve from time zero to the last detectable level calculations were performed using the linear trapezoidal rule.

Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

Outcome measures

Measure	Treatment A n=83 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=164 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=84 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=84 Participants Symbicort with charcoal (320 ug budesonide)
AUC0-t of Formoterol With and Without Charcoal Blockade	47.4 pg*h/mL Geometric Coefficient of Variation 26.0	40.1 pg*h/mL Geometric Coefficient of Variation 58.6	44.7 pg*h/mL Geometric Coefficient of Variation 26.8	34.5 pg*h/mL Geometric Coefficient of Variation 78.1

PRIMARY outcome

Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)

Population: PK population included subjects who had received both test and reference for at least one dose of each treatment without or with oral charcoal.

Maximum plasma level of budesonide with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

Outcome measures

Measure	Treatment A n=83 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=164 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=84 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=84 Participants Symbicort with charcoal (320 ug budesonide)
Cmax of Budesonide With and Without Charcoal Blockade	1040 pg/mL Geometric Coefficient of Variation 67.7	482 pg/mL Geometric Coefficient of Variation 63.4	1090 pg/mL Geometric Coefficient of Variation 78.9	542 pg/mL Geometric Coefficient of Variation 62.4

PRIMARY outcome

Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)

Population: PK population included subjects who had received both test and reference for at least one dose of each treatment without or with oral charcoal.

Maximum plasma level of formoterol with and without charcoal blockade. Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

Outcome measures

Measure	Treatment A n=83 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=164 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=84 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=84 Participants Symbicort with charcoal (320 ug budesonide)
Cmax of Formoterol With and Without Charcoal Blockade	11.9 pg/mL Geometric Coefficient of Variation 38.6	9.53 pg/mL Geometric Coefficient of Variation 57.5	12.4 pg/mL Geometric Coefficient of Variation 35.5	10.6 pg/mL Geometric Coefficient of Variation 58.4

SECONDARY outcome

Timeframe: 0-30 min (0, 2, 5, 10, 15, 20, and 30 min)

Population: PK population included subjects who had received both test and reference for at least one dose of each treatment without or with oral charcoal.

Area under the plasma concentration-time curve from time zero to 30 minutes calculations were performed using the linear trapezoidal rule.

Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

Outcome measures

Measure	Treatment A n=83 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=164 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=84 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=84 Participants Symbicort with charcoal (320 ug budesonide)
AUC0-30 of Budesonide With and Without Charcoal Blockade.	324 pg*h/mL Geometric Coefficient of Variation 36.5	174 pg*h/mL Geometric Coefficient of Variation 62.0	342 pg*h/mL Geometric Coefficient of Variation 38.3	193 pg*h/mL Geometric Coefficient of Variation 63.4

SECONDARY outcome

Timeframe: 0-30 min (0, 2, 5, 10, 15, 20, and 30 min)

Population: PK population included subjects who had received both test and reference for at least one dose of each treatment without or with oral charcoal.

Area under the plasma concentration-time curve from time zero to 30 minutes calculations were performed using the linear trapezoidal rule.

Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

Outcome measures

Measure	Treatment A n=83 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=164 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=84 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=84 Participants Symbicort with charcoal (320 ug budesonide)
AUC0-30 of Formoterol With and Without Charcoal Blockade.	3.85 pg*h/mL Geometric Coefficient of Variation 33.0	3.12 pg*h/mL Geometric Coefficient of Variation 54.4	4.00 pg*h/mL Geometric Coefficient of Variation 32.1	3.35 pg*h/mL Geometric Coefficient of Variation 58.2

SECONDARY outcome

Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)

Population: PK population included subjects who had received both test and reference for at least one dose of each treatment without or with oral charcoal.

Area under the plasma concentration-time curve from time zero to infinity calculations were performed using the linear trapezoidal rule.

Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

Outcome measures

Measure	Treatment A n=83 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=163 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=84 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=84 Participants Symbicort with charcoal (320 ug budesonide)
AUC0-∞ of Budesonide With and Without Charcoal Blockade	1980 pg*h/mL Geometric Coefficient of Variation 20.5	1450 pg*h/mL Geometric Coefficient of Variation 48.8	1900 pg*h/mL Geometric Coefficient of Variation 22.4	1410 pg*h/mL Geometric Coefficient of Variation 50.1

SECONDARY outcome

Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)

Population: PK population included subjects who had received both test and reference for at least one dose of each treatment without or with oral charcoal.

Area under the plasma concentration-time curve from time zero to infinity calculations were performed using the linear trapezoidal rule.

Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

Outcome measures

Measure	Treatment A n=61 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=126 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=75 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=63 Participants Symbicort with charcoal (320 ug budesonide)
AUC0-∞ of Formoterol With and Without Charcoal Blockade	56.0 pg*h/mL Geometric Coefficient of Variation 28.2	49.8 pg*h/mL Geometric Coefficient of Variation 57.1	54.5 pg*h/mL Geometric Coefficient of Variation 27.7	45.2 pg*h/mL Geometric Coefficient of Variation 61.6

SECONDARY outcome

Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)

Population: PK population included subjects who had received both test and reference for at least one dose of each treatment without or with oral charcoal.

Time at which the maximum plasma level (Cmax) occurred with and without charcoal blockade.

Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

Outcome measures

Measure	Treatment A n=83 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=164 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=84 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=84 Participants Symbicort with charcoal (320 ug budesonide)
Tmax for Budesonide With and Without Charcoal Blockade	0.08 hours Interval 0.03 to 0.75	0.25 hours Interval 0.03 to 1.5	0.08 hours Interval 0.03 to 0.75	0.25 hours Interval 0.03 to 1.0

SECONDARY outcome

Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)

Population: PK population included subjects who had received both test and reference for at least one dose of each treatment without or with oral charcoal.

Time at which the maximum plasma level (Cmax) occurred with and without charcoal blockade.

Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

Outcome measures

Measure	Treatment A n=83 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=164 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=84 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=84 Participants Symbicort with charcoal (320 ug budesonide)
Tmax for Formoterol With and Without Charcoal Blockade	0.08 hours Interval 0.08 to 0.2	0.08 hours Interval 0.04 to 0.25	0.08 hours Interval 0.03 to 0.17	0.08 hours Interval 0.08 to 0.17

SECONDARY outcome

Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)

Population: PK population included subjects who had received both test and reference for at least one dose of each treatment without or with oral charcoal.

Apparent elimination half-life calculated as 0.693/lambda zeta, with and without charcoal blockade.

Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

Outcome measures

Measure	Treatment A n=83 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=163 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=84 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=84 Participants Symbicort with charcoal (320 ug budesonide)
t1/2 for Budesonide With and Without Charcoal Blockade	2.90 hours Geometric Coefficient of Variation 17.0	2.94 hours Geometric Coefficient of Variation 19.8	2.79 hours Geometric Coefficient of Variation 17.0	2.80 hours Geometric Coefficient of Variation 15.8

SECONDARY outcome

Timeframe: 0-24h (0, 2, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 600, 720, and 1440 min)

Population: PK population included subjects who had received both test and reference for at least one dose of each treatment without or with oral charcoal.

Apparent elimination half-life calculated as 0.693/lambda zeta, with and without charcoal blockade.

Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

Outcome measures

Measure	Treatment A n=61 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=126 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=75 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=63 Participants Symbicort with charcoal (320 ug budesonide)
t1/2 for Formoterol With and Without Charcoal Blockade	9.57 hours Geometric Coefficient of Variation 29.3	9.33 hours Geometric Coefficient of Variation 35.2	10.09 hours Geometric Coefficient of Variation 29.8	9.15 hours Geometric Coefficient of Variation 33.6

SECONDARY outcome

Timeframe: At 75 min (1.25 hours) post-dose

Population: Safety population: all subjects who received at least one dose (2 inhalations) of investigational medicinal product

FEV1 refers to the volume of air that an individual can exhale during a forced breath in 1 second.

Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

and Symbicort 2, together. Please note that, within the safety population, 90 subjects received Treatment B. This would mean that theorically 180 participants received Symbicort 1 and Symbicort 2, together.

But some subjects were excluded from the statistical analysis for various reasons so that the total number included in the statistical anlysis for treatment B is 174.

Outcome measures

Measure	Treatment A n=84 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=174 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=87 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=86 Participants Symbicort with charcoal (320 ug budesonide)
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)	0.2 liters Standard Deviation 0.2	0.2 liters Standard Deviation 0.2	0.2 liters Standard Deviation 0.2	0.2 liters Standard Deviation 0.2

SECONDARY outcome

Timeframe: At 75 min (1.25 hours) post-dose

Population: Safety population: all subjects who received at least one dose (2 inhalations) of investigational medicinal product.

FVC = Forced vital capacity. It is the full amount of air that can be exhaled with effort in a complete breath.

FEV1/FVC = Tiffenau-Pinelli Index. This parameter represents the measurement of the amount of air an individual can forcefully exhale from his/her lungs.

Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.

Please note that, within the safety population, 90 subjects received Treatment B. This would mean that theorically 180 participants received Symbicort 1 and Symbicort 2, together.

But 6 subjects were excluded from the statistical analysis for various reasons so that the total number included in the statistical anlysis for treatment B is 174.

Outcome measures

Measure	Treatment A n=84 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=174 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=87 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=86 Participants Symbicort with charcoal (320 ug budesonide)
Change From Baseline in the Ratio of Forced Expiratory Volume in 1 Second to Forced Vital Capacity (FEV1/FVC)	3.7 ratio Standard Deviation 3.0	3.6 ratio Standard Deviation 3.4	3.2 ratio Standard Deviation 3.1	3.8 ratio Standard Deviation 3.2

SECONDARY outcome

Timeframe: At 75 min (1.25 hours) post-dose

Population: Safety population: all subjects who received at least one dose (2 inhalations) of investigational medicinal product.

PEFR is the highest rate at which gases can be expelled from the lungs via an open mouth. Its measurement is a simple procedure in which an individual takes a full inspiration and blows out as forcibly as possible into an instrument called a peak flow meter, which measures the maximal gas flow in an exhalation in liters per minute.

Participants for the Treatment B are counted for both Symbicort 1 and Symbicort 2, together.Please note that, within the safety population, 90 subjects received Treatment B. This would mean that theorically 180 participants received Symbicort 1 and Symbicort 2, together. But 6 subjects were excluded from the statistical analysis for various reasons so that the total number included in the statistical anlysis for treatment B is 174.

Outcome measures

Measure	Treatment A n=84 Participants Z7200 without charcoal (160 ug budesonide)	Treatment B n=174 Participants Symbicort 1+2 without charcoal (320 ug budesonide)	Treatment C n=87 Participants Z7200 with charcoal (160 ug budesonide)	Treatment D n=86 Participants Symbicort with charcoal (320 ug budesonide)
Change From Baseline in Peak Expiratory Flow Rate (PEFR)	22.2 L/min Standard Deviation 48.9	20.5 L/min Standard Deviation 38.7	24.8 L/min Standard Deviation 35.5	19.2 L/min Standard Deviation 38.9

Adverse Events

Treatment A

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Treatment B

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Treatment C

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Treatment D

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Treatment A n=84 participants at risk Z7200 without charcoal	Treatment B n=90 participants at risk Symbicort 1+2 without charcoal	Treatment C n=88 participants at risk Z7200 with charcoal	Treatment D n=86 participants at risk Symbicort with charcoal
Nervous system disorders Headache	6.0% 5/84 • Number of events 5 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	8.9% 8/90 • Number of events 8 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	2.3% 2/88 • Number of events 2 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	8.1% 7/86 • Number of events 7 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Nervous system disorders Migrane	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/90 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.2% 1/86 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Nervous system disorders Paraesthesia	1.2% 1/84 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/90 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Nervous system disorders Presyncope	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/90 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Gastrointestinal disorders Nausea	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/90 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.2% 1/86 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Gastrointestinal disorders Abdominal discomfort	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/90 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/88 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Gastrointestinal disorders Abdominal Pain Upper	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/90 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Gastrointestinal disorders Dyspepsia	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/90 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.2% 1/86 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Gastrointestinal disorders Oral Discomfort	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/90 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/88 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Gastrointestinal disorders Oral Pain	1.2% 1/84 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/90 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Gastrointestinal disorders Toothache	1.2% 1/84 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/90 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Gastrointestinal disorders Vomiting	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/90 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
General disorders Catheter site related reaction	1.2% 1/84 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/90 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
General disorders Chest discomfort	1.2% 1/84 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/90 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
General disorders Axillary pain	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/90 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.2% 1/86 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
General disorders Catheter site pain	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/90 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
General disorders Vessel puncture site swelling	1.2% 1/84 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/90 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/90 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.2% 1/86 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	2.2% 2/90 • Number of events 2 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/90 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/88 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	1.2% 1/84 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/90 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Respiratory, thoracic and mediastinal disorders Throat irritation	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/90 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.2% 1/86 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Investigations Eosinophil count increased	1.2% 1/84 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/90 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/88 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Investigations Alanine aminotransferase increased	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/90 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/88 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Investigations Blood creatine phosphokinase increased	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/90 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Investigations Blood pressure systolic increased	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/90 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.2% 1/86 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/90 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.2% 1/86 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Musculoskeletal and connective tissue disorders Pain in extremity	1.2% 1/84 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/90 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Musculoskeletal and connective tissue disorders Limb discomfort	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/90 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.2% 1/86 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Musculoskeletal and connective tissue disorders Muscle spasms	1.2% 1/84 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/90 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Musculoskeletal and connective tissue disorders Muscular Weakness	1.2% 1/84 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/90 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Musculoskeletal and connective tissue disorders Myalgia	1.2% 1/84 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/90 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Infections and infestations Gastroenteritis	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/90 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Infections and infestations Nasopharyngitis	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/90 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.2% 1/86 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Infections and infestations Thooth abscess	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/90 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Infections and infestations Upper respiratory tract infection	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/90 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Infections and infestations Viral upper respiratory tract infection	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/90 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Skin and subcutaneous tissue disorders Rash erythematous	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/90 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.2% 1/86 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Skin and subcutaneous tissue disorders Acne	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/90 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.2% 1/86 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Skin and subcutaneous tissue disorders Blister	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/90 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Skin and subcutaneous tissue disorders Rash	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/90 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Injury, poisoning and procedural complications Laceration	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/90 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Injury, poisoning and procedural complications Thermal Burn	1.2% 1/84 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/90 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Eye disorders Eye Pain	0.00% 0/84 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	1.1% 1/90 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Psychiatric disorders Euphoric mood	1.2% 1/84 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/90 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).
Reproductive system and breast disorders Dysmenorrhoea	1.2% 1/84 • Number of events 1 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/90 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/88 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).	0.00% 0/86 • Throughout the study till the end of trial assessment, which was completed on Day 2 of last treatment period (up to 6 weeks).

Additional Information

Isabella Salerio, PhD

Zambon SpA

Phone: +39 02665241

Email: clinicaltrials@zambongroup.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place